Synthesis
General procedure for the synthesis of 3-amino-n-butanol from 3-aminobutyric acid: a general synthesis of β-amino acids was used. A solution of borane-tetrahydrofuran complex (1 M, 3-4 mL/mmol, equivalent to 3-11 equivalents of β-amino acids) was slowly added dropwise to β-amino acids (1 equivalent, 1 mL/mmol) suspended in THF over a period of 1 h at 0 °C. The reaction was carried out by stirring the mixture for 20 min at room temperature. After the dropwise addition was completed, the reaction mixture was stirred at room temperature for 20 minutes, followed by heating and refluxing for 22 hours. Upon completion of the reaction, the mixture was cooled to 0 °C and methanol (2 mL/mmol) was added over 30 min. Next, the mixture was heated to reflux for 20 minutes and concentrated to obtain a thick oily substance. This oily substance was co-evaporated with methanol (3 x 200 mL) and the solid obtained was dried under vacuum to give the target product 3-substituted 3-amino-1-propanol derivative as a white waxy solid (quantitative yield).
A 48% aqueous HBr solution (2 mL/equivalent) was slowly added to a flask containing 3-substituted 3-amino-1-propanol (1 equivalent). The mixture was heated and refluxed for 6 h and then concentrated to dryness, and the resulting crude product was used directly in the next step of the reaction.
The 1-substituted 3-bromo-1-propanamine hydrobromide obtained in step 2 was added to a solution of water and 1,4-dioxane containing sodium sulfite (1.0 eq.). The mixture was heated under reflux conditions for 6 hours and subsequently concentrated to dryness. The residue was treated with concentrated HCl and after filtration to remove inorganic material, the filtrate was treated with ethanol to precipitate the corresponding sulfonic acid. The crude sulfonic acid was suspended in ethanol and heated at reflux for 1 hour. After cooling to room temperature, the solid was collected by filtration, washed with ethanol and dried overnight in a vacuum oven at 60°C to give 3-substituted 3-amino-1-propanesulfonic acid as a fine white crystalline solid.
References
[1] Patent: US2006/223855, 2006, A1. Location in patent: Page/Page column 171
[2] Patent: EP1820799, 2007, A1
[3] Organic Letters, 2017, vol. 19, # 17, p. 4696 - 4699
[4] Patent: US2005/54701, 2005, A1
[5] Journal of Heterocyclic Chemistry, 2007, vol. 44, # 6, p. 1465 - 1473
